SLC3A2, antigen of mAb 3G9, promotes migration and invasion by upregulating of mucins in gastric cancer.
SLC3A2, antigen of mAb 3G9, promotes migration and invasion by upregulating of mucins in gastric cancer.
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DOI：
10.18632/oncotarget.19529
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发表时间：
2017-10-24
期刊：
影响因子：
--
通讯作者：
Ji J
中科院分区：
文献类型：
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作者：
Wang S;Han H;Hu Y;Yang W;Lv Y;Wang L;Zhang L;Ji J
据报道，溶质载体家族3成员2 （SLC3A2）在多种癌症中高表达。然而，SLC3A2在胃癌（GC）中的功能尚未得到很好的探讨。单克隆抗体（mAb） 3G9是由多种人胃癌细胞系的免疫原产生的，已被证明与胃癌组织特异性结合。本研究确定了mAb 3G9的靶抗原为SLC3A2，并检测了SLC3A2在胃癌细胞系和胃癌组织中的表达谱。我们发现SLC3A2的表达增加与GC患者的浆膜侵袭有关。敲除SLC3A2可抑制BGC-823细胞在体外和体内的迁移和侵袭，而在NCI-N87细胞中过表达SLC3A2可促进BGC-823细胞在体外和体内的迁移和侵袭。机制研究表明MUC1、MUC16和MUC5B是胃癌细胞SLC3A2的下游基因。综上所述，我们的数据表明，SLC3A2通过上调几个粘蛋白基因的表达来促进胃癌的侵袭性表型，可能作为诊断和靶向治疗的潜在生物标志物。
Solute carrier family 3 member 2 (SLC3A2) has been reported to be highly expressed in a variety of carcinomas. However, the function of SLC3A2 in gastric carcinoma (GC) has not been well explored. Monoclonal antibody (mAb) 3G9, generated from immunogen of various human GC cell lines, has been shown to bind to GC tissues specifically. In this study, we identified the target antigen of mAb 3G9 as SLC3A2, and detected the expression profile of SLC3A2 in a panel of gastric cancer cell lines and GC tumor tissues. We found that the increased expression of SLC3A2 was associated with serosal invasion in GC patients. Knockout of SLC3A2 suppressed the migration and invasion of BGC-823 cells in vitro and in vivo, whereas overexpression of SLC3A2 in NCI-N87 cells promoted the migration and invasion in vitro and in vivo. Mechanistic investigations suggested that MUC1, MUC16 and MUC5B were the downstream genes of SLC3A2 in GC cells. Taken together, our data suggested that SLC3A2 promoted the aggressive phenotype of GC by upregulating several mucin genes expression and may serve as a potential biomarker for diagnosis and target therapy.